Carbidopa-Levodopa

Aka: Carbidopa-Levodopa, Levodopa, Carbidopa/Levodopa, Levodopa-Carbidopa, Levodopa/Carbidopa, Sinemet, Stalevo, Dopa decarboxylase inhibitor, Dopamine Precursor, Rytary, Duopa, Inbrija

II. Precautions: General pointers

  1. Sinemet (regular release) is by far the single most effective agent
    1. This agent should be the first line and main agent used for Parkinsonism
    2. All other agents are adjuncts only
  2. Dosing Threshold
    1. Identify the individual patient's optimal dose and use this dose at each dosing interval
    2. Using a lower dose below threshold will be inadequate
  3. Food Interactions
    1. Take at least one hour before a meal or 2 hours after a meal
  4. Wearing off of effect
    1. See frequency of dosing of Sinemet below
    2. Most common cause of Insomnia
    3. May cause anxiety, nocturnal cramps
  5. Dyskinesia (e.g. Choreiform movements)
    1. Dyskinesia is more age related than that of duration of Levodopa use
    2. Reducing each Levodopa dose decreases this adverse effect
    3. Amantadine decreases Dyskinesia
  6. Adverse Effects: Educate patients about serious effects (most are reduced by tapering dose)
    1. Drowsiness
    2. Pathologic Gambling, Hypersexuality, Excessive shopping/spending
    3. Hallucinations or Delusions
    4. Swelling

III. Preparations

  1. Carbidopa/Levodopa (Sinemet)
    1. Preferred option over sustained release
      1. Lower cost
      2. Better pharmacokinetics
      3. Less Drug Interactions
    2. Start at 25/100 orally three times daily
    3. Increase by one tablet every 1-2 days as needed
    4. Maximum : 3 tablets per dose, three times daily (no benefit to higher doses, but frequency may be increased)
    5. Frequency of dose
      1. Initially give dose three times daily
      2. Long term, dose may wear off early
        1. Frequency may need to be increased to every 6 hours (at same number of tablets at each dose)
  2. Carbidopa/Levodopa Sustained release (Sinemet CR)
    1. Start at 50/200 orally twice daily
    2. Increase by one tablet every 3 days as needed
    3. Maximum : 8 tablets daily
    4. No benefit over immediate release in motor function, and absorption may be sporadic in some patients
  3. Carbidopa/Levodopa fast onset, sustained release (Rytary)
    1. Onset within 1 hour, duration of 6 hours
    2. Start with lowest dose taken 3 times daily
    3. Costs 3-4 times more than generic Carbidopa/Levodopa
    4. May decrease "off time", the wearing off of activity between doses
    5. Consider in advanced Parkinsonism for "off time" problems despite four time daily dosing
    6. Typical Dose: 3-4 caps three times daily
    7. Requires higher dosing than other preparations due to lower bioavailability
    8. (2015) Presc Lett 22(7): 41
  4. Carbidopa/Levodopa/Entacapone (Stalevo)
    1. Start at 12.5/50/200 PO bid
    2. Increase slowly
    3. Maximum : 8 tablets daily
  5. Carbidopa/Levodopa Enteral Suspension (Duopa)
    1. Convert from immediate release dosing to administer over 16 hours (max daily dose 2000 mg)
  6. Inbrija (inhaled Levodopa)
    1. Indicated in off-time motor rigidity or Tremor
    2. Rapid onset (10 min after inhalation) and duration of 1 hour used for prn "off time" rigidity or Tremor
    3. Less expensive ($30/dose) than Apokyn ($200/dose), an injectable option for off-time
    4. Requires dexterity to replace capsule in Inhaler
    5. Avoid in underlying lung disease (e.g. Asthma, COPD) due to bronchospasm risk
    6. (2019) Presc Lett 26(5)

IV. Adverse Effects

  1. Nausea
  2. Somnolence
  3. Hallucinations
  4. Dizziness or Orthostasis
  5. Delusions
  6. Dyskinesias
  7. Lower extremity edema
  8. Major Depression and Suicidal Ideation

V. References

  1. Ahlskog (2011) Mayo Internal Medicine Review Lecture
  2. Schim (2001) CMEA Medicine Lecture, San Diego
  3. Clarke (2003) Clin Evid 10:1582-98 [PubMed]
  4. Clarke (2004) Lancet Neurol 3:466-74 [PubMed]
  5. Gazewood (2013) Am Fam Physician 87(4): 267-73 [PubMed]
  6. Halli-Tierney (2020) Amf fam Physician 102(11):679-91 [PubMed]
  7. Nutt (2005) N Engl J Med 353:1021-7 [PubMed]
  8. Olanow (2001) Neurology 56:S1-88 [PubMed]
  9. Rao (2006) Am Fam Physician 74:2046-56 [PubMed]
  10. Young (1999) Am Fam Physician 59(8):2155-67 [PubMed]

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Related Studies

Cost: Medications

carbidopa-levodopa (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
CARBIDOPA-LEVODOPA 10-100 TAB Generic $0.15 each
CARBIDOPA-LEVODOPA 25-100 TAB Generic $0.10 each
CARBIDOPA-LEVODOPA 25-250 TAB Generic $0.18 each
CARBIDOPA-LEVODOPA-ENTA 100 MG Generic $1.90 each
CARBIDOPA-LEVODOPA-ENTA 125 MG Generic $1.82 each
CARBIDOPA-LEVODOPA-ENTA 150 MG Generic $1.59 each
CARBIDOPA-LEVODOPA-ENTA 200 MG Generic $2.25 each
CARBIDOPA-LEVODOPA-ENTA 50 MG Generic $1.93 each
CARBIDOPA-LEVODOPA-ENTA 75 MG Generic $1.85 each
sinemet (on 6/8/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
SINEMET 25-100 MG TABLET Generic $0.10 each
stalevo (on 1/4/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
STALEVO 100 TABLET Generic $1.90 each
STALEVO 150 TABLET Generic $1.59 each
STALEVO 200 TABLET Generic $2.25 each
rytary (on 3/22/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
RYTARY ER 23.75 MG-95 MG CAP $2.47 each
RYTARY ER 36.25 MG-145 MG CAP $2.48 each
RYTARY ER 48.75 MG-195 MG CAP $2.47 each
RYTARY ER 61.25 MG-245 MG CAP $3.12 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information.

Ontology: Levodopa (C0023570)

Definition (NCI) An amino acid precursor of dopamine with antiparkinsonian properties. Levodopa is a prodrug that is converted to dopamine by DOPA decarboxylase and can cross the blood-brain barrier. When in the brain, levodopa is decarboxylated to dopamine and stimulates the dopaminergic receptors, thereby compensating for the depleted supply of endogenous dopamine seen in Parkinson's disease. To assure that adequate concentrations of levodopa reach the central nervous system, it is administered with carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, thereby diminishing the decarboxylation and inactivation of levodopa in peripheral tissues and increasing the delivery of dopamine to the CNS.
Definition (MSH) The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.
Definition (CSP) naturally occuring form of DOPA and precursor of dopamine; used as an antiparkinsonian agent; unlike dopamine it can be administered orally.
Definition (PDQ) An amino acid precursor of dopamine with antiparkinsonian properties. Levodopa is a prodrug that is converted to dopamine by DOPA decarboxylase and can cross the blood-brain barrier. When in the brain, levodopa is decarboxylated to dopamine and stimulates the dopaminergic receptors, thereby compensating for the depleted supply of endogenous dopamine seen in Parkinson's disease. To assure that adequate concentrations of levodopa reach the central nervous system, it is administered with carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, thereby diminishing the decarboxylation and inactivation of levodopa in peripheral tissues and increasing the delivery of dopamine to the CNS. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42622&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42622&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C611" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Neuroreactive Substance or Biogenic Amine (T124) , Amino Acid, Peptide, or Protein (T116)
MSH D007980
SnomedCT 15383004, 387086006, 65955006
LNC LP32555-2, LP16328-4, MTHU015998
English L-3,4-Dihydroxyphenylalanine, L-Dopa, Levodopa, 3 Hydroxy L tyrosine, 3-Hydroxy-L-tyrosine, L 3,4 Dihydroxyphenylalanine, (--)-3-(3,4-Dihydroxyphenyl)-L-alanine, beta-(3,4-Dihydroxyphenyl)-L-alanine, (--)-2Amino-3-)3,4-dihydroxyphenyl)propanoic Acid, DOPA A L, levodopa, LEVODOPA, Levodopa [Chemical/Ingredient], l-dopa, l dopa levodopa, dopa l, l dopa, L 3,4-dihydroxyphenylalanine, (--)-2Amino-3-(3,4-dihydroxyphenyl)propanoic Acid, L-DOPA, .beta.-(3,4-Dihydroxyphenyl)-L-alanine, L-.beta.-(3,4-Dihydroxyphenyl)alanine, (-)-3-(3,4-Dihydroxyphenyl)-L-alanine, L(-)-Dopa, 3-(3,4-Dihydroxyphenyl)-L-alanine, L-dopa, L-3-hydroxytyrosine, L-Dopa - Levodopa, L-dopa preparation, Levodopa (product), Levodopa (substance), L Dopa
Swedish Levodopa
Czech levodopa
Spanish L-dopa, L-3-hidroxitirosina, levo-dopa, levodopa (producto), levodopa (sustancia), levodopa, preparado de L-dopa, L-Dopa, Levodopa
Finnish Levodopa
Russian LEVODOFA, LEVODOPA, L-DOFA, L-DOPA, L-ДОФА, ЛЕВОДОПА, ЛЕВОДОФА
French 3-Hydroxy-L-tyrosine, L-Dopa, Lévodopa
German DOPA A L, L-Dopa, Levodopa
Croatian LEVODOPA
Polish Lewodopa, L-dopa
Japanese L-ジオキシフェニルアラニン, L-ドーパ, ドパストン, ドパール, レボドパ, レボドーパ, Lド-パ, Lドパ
Italian Levodopa
Portuguese L-Dopa, Levodopa
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Sinemet (C0074559)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C009265
English Sinemet, BMS brand of carbidopa, levodopa drug combination, sinemet
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Carbidopa / Levodopa (C0353697)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
SnomedCT 323113004, 372605005, 346377002, 404830004
English Levodopa with carbidopa, CARBIDOPA/LEVODOPA, carbidopa + levodopa, carbidopa + levodopa (medication), Carbidopa-Levodopa, carbidopa-levodopa, Carbidopa / Levodopa, levodopa carbidopa, carbidopa levodopa, co careldopa, co-careldopa, levodopa with carbidopa, Levodopa with carbidopa (product), Co-careldopa (substance), Co-careldopa (product), Carbidopa+levodopa (product), Carbidopa+levodopa, Levodopa with carbidopa (substance), Carbidopa and Levodopa, Co-careldopa
Spanish levodopa con carbidopa, co-careldopa (producto), levodopa-carbidopa, levodopa-carbidopa (sustancia), levodopa con carbidopa (producto), co-careldopa, co-careldopa (sustancia), carbidopa + levodopa (producto), carbidopa + levodopa
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Carbidopa / entacapone / Levodopa (C1329991)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
SnomedCT 410860008
English CARBIDOPA/LEVODOPA/ENTACAPONE @ @ UNIDENTIFIED, CARBIDOPA/LEVODOPA/ENTACAPONE UNIDENTIFIED, CARBIDOPA/ENTACAPONE/LEVODOPA, carbidopa + levodopa + entacapone, carbidopa + levodopa + entacapone (medication), Carbidopa / entacapone / Levodopa, Carbidopa/Entacapone/Levodopa, carbidopa/entacapone/levodopa, Carbidopa+levodopa+entacapone (product), Carbidopa+levodopa+entacapone, Levodopa+careldopa+entacapone
Spanish carbidopa+levodopa+entacapona (producto), carbidopa+levodopa+entacapona
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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